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Echinococcus granulosus protoscoleces promotes proliferation and invasion of hepatocellular carcinoma cells

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Abstract

There may exist a connection between Echinococcus granulosus infection and cancer development. Here, it is aimed to investigate specific effects of E. granulosus protoscoleces (PSCs) on the proliferation and invasion capacities of hepatocellular carcinoma (HCC) cells in vitro and ex vitro. HepG2 cells were cultured with different quantities of E. granulosus PSCs in vitro. MTT analysis was used to evaluate effects of E. granulosus PSCs on the proliferation of HepG2 cells. Besides, scratch and transwell assays were respectively used for the detection of HepG2 cells migration and invasion capacities after co-culture with E. granulosus PSCs. Then, HepG2 cells were subcutaneously transplanted into nude mice with or without E. granulosus PSCs. From the 25th day of transplantation, the volume of subcutaneous lesions was measured every four days. At the 37th day, subcutaneous lesions were removed and their weight was evaluated. H&E staining was used for detecting basic pathological changes. HepG2 cells grew well without obvious morphological changes. Proliferation rate and migration capacity of HepG2 cells were higher in the co-culture group than the control group, which was closely associated with quantities of E. granulosus PSCs and co-culture time length. Moreover, HepG2 cells co-cultured with E. granulosus PSCs had stronger invasion ability than the control HepG2 cells. Importantly, there existed significant differences in the volume and weight of subcutaneous lesions after transplanting HepG2 cells with E. granulosus PSCs than the control group. HepG2 cells were also more pathologically heterogeneous in morphology after transplantation with E. granulosus PSCs. Thus, E. granulosus PSCs may promote proliferation and invasion of HCC cells.

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References

  • Akgül H, Tez M, Unal AE et al (2003) Echinococcus against cancer: why not? Cancer 98:1999–2000

    Article  Google Scholar 

  • Aliyali M, Badali H, Shokohi T et al (2016) Coinfection of pulmonary hydatid cyst and Aspergilloma: case report and systematic review. Mycopathologia 181:255–265

    Article  Google Scholar 

  • Alvarez DE, Medeiros A, Miguez M et al (2001) O-glycosylation in Echinococcus granulosus: identification and characterization of the carcinoma-associated Tn antigen. Exp Parasitol 98:100–109

    Article  Google Scholar 

  • Amri M, Touil-Boukoffa C (2015) Particles from the Echinococcus granulosus laminated layer inhibit CD40 upregulation in dendritic cells by interfering with Akt activation. Acta Trop 149:186–194

    Article  CAS  Google Scholar 

  • Atayde VD, Jasiulionis MG, Cortez M et al (2008) A recombinant protein based on Trypanosoma cruzi surface molecule gp82 induces apoptotic cell death in melanoma cells. Melanoma Res 18:172–183

    Article  CAS  Google Scholar 

  • Bangaru SD, Kozarsky PE, Lee DJ et al (2015) A bystander effect of lung cancer chemotherapy on chronic Echinococcal disease. World J Oncol 6:416–420

    Article  Google Scholar 

  • Baz A, Carol H, Fernandez V et al (2008) Echinococcus granulosus: induction of T-independent antibody response against protoscolex glycoconjugates in early experimental infection. Exp Parasitol 119:460–466

    Article  CAS  Google Scholar 

  • Berriel E, Russo S, Monin L et al (2013) Antitumor activity of human hydatid cyst fluid in a murine model of colon cancer. Sci World J 2013:230176. https://doi.org/10.1155/2013/230176

    Article  CAS  Google Scholar 

  • Chookami MB, Sharafi SM, Sefiddashti RR et al (2016) Effect of two hydatid cyst antigens on the growth of melanoma cancer in C57/ black mice. J Parasit Dis 40:1170–1173

    Article  Google Scholar 

  • Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  CAS  Google Scholar 

  • Craig PS, McManus DP, Lightowlers MW et al (2007) Prevention and control of cystic echinococcosis. Lancet Infect Dis 7:385–394

    Article  Google Scholar 

  • Dang LH, Bettegowda C, Huso DL et al (2001) Combination bacteriolytic therapy for the treatment of experimental tumors. Proc Natl Acad Sci USA 98:15155–15160

    Article  CAS  Google Scholar 

  • De MC, Ferlay J, Franceschi S et al (2012) Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 13:607–615

    Article  Google Scholar 

  • Dixon JB, Jenkins P (1995) Immunology of mammalian metacestode infection. II. Antigens, protective immunity and immunopathology. Helm Abs Ser 64:599–613

    Google Scholar 

  • Dunn GP, Old LJ, Schreiber RD (2004) The three Es of cancer immunoediting. Annu Rev Immunol 22:329–360

    Article  CAS  Google Scholar 

  • Guan W, Zhang XQ, Wang X et al (2019) Employing parasite against cancer: a lesson from the canine tapeworm Echinococcus granulocus. Front Pharmacol 10:1137. https://doi.org/10.3389/fphar.2019.01137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gottstein B, Soboslay P, Ortona E et al (2017) Immunology of alveolar and Cystic echinococcosis (AE and CE). Adv Parasitol 96:1–54. https://doi.org/10.1016/bs.apar.2016.09.005

    Article  CAS  PubMed  Google Scholar 

  • Hsu YC, Ho HJ, Lee TY et al (2018) Temporal trend and risk determinants of hepatocellular carcinoma in chronic hepatitis B patients on entecavir or tenofovir. J Viral Hepat 25:543–551

    Article  CAS  Google Scholar 

  • Jiang Y, Zhou ZJ, Fei R et al (2019) Role of miR-182-5p overexpression in trichloroethylene-induced abnormal cell cycle functions in human HepG2 cells. J Toxicol Environ Health 82:920–927

    Article  CAS  Google Scholar 

  • Klinkert MQ, Heussler V (2006) The use of anticancer drugs in antiparasitic chemotherapy. Mini Rev Med Chem 6:131–143

    Article  CAS  Google Scholar 

  • Li H, Song T, Shao Y et al (2015) Cystic echinococcosis accompanied by hepatocellular carcinoma in a female herdsman. Int J Clin Exp Med 8:2985–2988

    PubMed  PubMed Central  Google Scholar 

  • Li ZD, Zhang CS, Li L et al (2019) The local immune response during Echinococcus granulosus growth in a quantitative hepatic experimental model. Sci Rep 9:19612. https://doi.org/10.1038/s41598-019-56098-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang CC, Park AY, Guan JL (2007) In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protocols 2:329–333

    Article  CAS  Google Scholar 

  • Noya V, Bay S, Festari MF et al (2013) Mucin-like peptides from Echinococcus granulosus induce antitumor activity. Int J Oncol 43:775–784

    Article  CAS  Google Scholar 

  • Morimoto T, Nishigaki-Maki K, Ohno K et al (2000) Transplantation of xenogeneic embryonic thymus to athymic nude mice induces acquisition of distorted immunity. Transplant Proc 32:956–957

    Article  CAS  Google Scholar 

  • Oikonomopoulou K, Brinc D, Kyriacou K et al (2013) Infection and cancer: revaluation of the hygiene hypothesis. Clin Cancer Res 19:2834–2841

    Article  CAS  Google Scholar 

  • Qi X, Miaomiao Y, Huanping L et al (2019) In vitro efficacy of ampelopsin against Echinococcus granulosus and Echinococcus multilocularis. J Vet Med Sci 81:1853–1858

    Article  Google Scholar 

  • Ran B, Aimaiti Y, Shao YM et al (2020) Co-existence of hepatocellular carcinoma and cystic echinococcosis. Infect Agent Cancer 15:5. https://doi.org/10.1186/s13027-020-0275-0

    Article  CAS  Google Scholar 

  • Sznol M, Lin SL, Bermudes D et al (2000) Use of preferentially-replicating bacteria for the treatment of cancer. J Clin Investig 105:1027–1030

    Article  CAS  Google Scholar 

  • Turhan N, Esendagl G, Ozkayar O et al (2015) Co-existence of Echinococcus granulosus infection and cancer metastasis in the liver correlates with reduced Th1 immune responses. Parasite Immunol 37:16–22

    Article  CAS  Google Scholar 

  • Wen H, Vuitton L, Tuxun T, et al (2019) Echinococcosis in the 21st century. Clinic Microbiol Rev 32: e0005–18. https://doi.org/10.1128/CMR.00075-18

    Article  Google Scholar 

  • Yamada T, Goto M, Punj V et al (2002) The bacterial redox protein azurin induces apoptosis in J774 macrophages through complex formation and stabilization of the tumor suppressor protein p53. Infect Immun 70:7054–7062

    Article  CAS  Google Scholar 

  • Yousofi DH, Soozangar N, Khorami S et al (2012) Hydatid cyst protoscolices induce cell death in WEHI-164 fibrosarcoma cells and inhibit the proliferation of baby hamster kidney fibroblasts in vitro. J Parasitol Res 2012:304183. https://doi.org/10.1155/2012/304183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang WB, Jones MK, Li J et al (2005) Echinococcus granulosus: pre-culture of protoscoleces in vitro signifificantly increases development and viability of secondary hydatid cysts in mice. Exp Parasitol 110:88–90

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Hepatobiliary and Hydatid Disease Department, Digestive and Vascular Surgery Center, First Affiliated Hospital of Xinjiang Medical University for the technical support.

Funding

This study was supported by the Key Laboratory Open Research Program of State Key Laboratory on Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia [Grant number: SKL-HIDCA-2017-1] and the National Major Science and Technology Project of China [Grant Number: 2018ZX10301201].

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AY: conception and design; acquisition of data; analysis and interpretation of data; drafting the article. MW: conception and design; acquisition of data; Analysis and interpretation of data. BR: Conception and design; Acquisition of data; Analysis and interpretation of data. GL: conception and design; acquisition of data; Analysis and interpretation of data. TA: conception and design; Final approval of the version to be submitted. HX: conception and design; provision of study material. YS: conception and design; provision of study material. HW: conception and design; provision of study material; final approval of the version to be submitted.

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Correspondence to Hui Xiao, Yingmei Shao or Hao Wen.

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Yasen, A., Wang, M., Ran, B. et al. Echinococcus granulosus protoscoleces promotes proliferation and invasion of hepatocellular carcinoma cells. Cytotechnology 73, 13–22 (2021). https://doi.org/10.1007/s10616-020-00437-0

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